RONALD WILSON REAGAN / 1911-2004

Search Is On for Alzheimer's Cure as Boomers Age

In the 10 years since Ronald Reagan hand-penned his poignant letter to the American people disclosing his diagnosis of Alzheimer's disease, great scientific progress has been made in understanding the nature of the affliction, but few of the findings have made their way into clinical practice.

Five drugs are now available in the United States that provide some relief of symptoms -- and dozens more are under study. An experimental vaccine against Alzheimer's proved toxic in humans, but researchers are studying an improved version.

Small preliminary studies hint that gene therapy or implants of new brain cells may slow the course of the disease, but such approaches are years away from wide use.

Stem cell research, in particular, has been slow because of controversies surrounding the use of stem cells taken from human embryos. In May, Nancy Reagan made a plea for an acceleration in such research, saying that it could lead to a cure for people like her husband.

Federal research funding devoted to Alzheimer's has jumped from $298 million in 1994 to more than $650 million in the current fiscal year. The Alzheimer's Assn. has been lobbying for a $40-million increase in this year's funding and has a goal of $1 billion per year for the disease.

But it is still a race against time.

"There have been great increases in the amount of information, and it's an accelerating process," says Bill Thies, vice president for medical and scientific affairs for the Alzheimer's Assn.. "We are moving in the right direction, but it's clear that we aren't finished yet."

What worries experts the most is the explosion of cases that will almost certainly occur in the coming years with the aging of the baby boom population. Without a cure or more effective treatment -- the therapies available provide only moderate symptomatic relief, with no effect on the causes -- Alzheimer's will burgeon into a major public health problem.

Alzheimer's is a brain disorder that gradually destroys a person's memory. The number of people developing this affliction is expected to more than triple from the current 4.5 million to 16 million by the year 2050 -- when every baby boomer will have turned 85.

Researchers are probing the mysteries of Alzheimer's on many fronts. Among them:

* Brain cell regeneration: Most scientists believed that once a brain nerve cell died, it could not be replaced, and its function was lost forever. Their thinking has since changed, the result of studies in mice and monkeys that have shown cell regeneration, leading them to feel more optimistic about new cell growth, and the possibility of applying this knowledge to Alzheimer's disease.

One potential approach focuses on a substance in the brain called nerve growth factor. Scientists aren't yet sure exactly how nerve growth factor works; however, it is known to be one of several such neurotrophic factors in the brain. Although nerve cells in the brain cannot divide, they can repair themselves after injury, and neurotrophic factors promote this regeneration.

Researchers at UC San Diego in April reported results from an eight-patient study that suggested gene therapy increasing the concentration of nerve growth factor in the brain could slow the progression of the disease. They took skin cells from the patients, inserted the gene for nerve growth factor, then implanted the cells into brain regions affected by Alzheimer's. Although the purpose of the study was to determine the safety of the procedure, Dr. Mark H. Tuszynski and his colleagues found that deterioration of the patient's faculties slowed after the procedure.

* Diagnosis: There is no laboratory test that can diagnose Alzheimer's. But researchers such as Dr. Gary W. Small, director of the UCLA Center on Aging, have shown that positron emission tomography, or PET, scanning can accurately detect Alzheimer's in its early stages.

* Drugs: This is regarded as a crucial area of exploration. Five drugs have been approved by the Food and Drug Administration for the treatment of Alzheimer's disease: tacrine (Cognex); donepezil (Aricept); rivastigmine (Exelon); galantamine (Reminyl); and memantine (Namenda). Tacrine was the first to be approved but is rarely used anymore because of the possibility of serious side effects, including liver damage.

Tacrine, donepezil, rivastigmine and galantamine belong to a class of drugs called cholinesterase inhibitors. Each acts in a different way to block the breakdown of acetylcholine, a brain chemical that is important for memory. Memantine shields the brain from overexposure to another neurochemical called glutamate. High levels of glutamate associated with Alzheimer's kill brain cells.

Each of the drugs provide limited benefits to select groups of patients, but none provides dramatic results in delaying the course of the disease. All cost about $120 per month, and more than 1 million Americans are taking them regularly.